rs2684792

Positions:

• chr15-98944852-G-A
• chr15-98944852-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.3587+1800G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,144 control chromosomes in the GnomAD database, including 21,099 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21099 hom., cov: 34)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

Genes affected

IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3587+1800G>A		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3587+1800G>A		intron_variant			NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000649865.1	c.3584+1800G>A		intron_variant				ENSP00000496919	A1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77086 AN: 152028 Hom.: 21079 Cov.: 34

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.530

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.507 AC: 77128 AN: 152144 Hom.: 21099 Cov.: 34 AF XY: 0.503 AC XY: 37439 AN XY: 74398

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.536

Alfa AF: 0.595 Hom.: 54184

Bravo AF: 0.496

Asia WGS AF: 0.440 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2684792; hg19: chr15-99488081;